Formation, reactions and toxicity of aldehydes produced in the course of lipid peroxidation in cellular membranes

Abstract

The formation, reactivity and toxicity of aldehydes originating from the peroxidation of lipids of cellular membranes are reviewed. Very reactive aldehydes, namely 4-hydroxyalkenals, were first shown to be formed in autoxidizing chemical systems. It was subsequently shown that 4-hydroxyalkenals, and particularly 4-hydroxynonenal, are formed in substantial amounts under biological conditions, i.e. during the peroxidation of lipids of liver microsomes incubated in the NADPH-Fe system. Many other aldehydes were then identified in peroxidizing liver microsomes or hepatocytes: alkanals (hexanal the most represented), alk-2-enals and 4-hydroxyalkenals (4-hydroxynonenal and 4,5-dihydroxydecenal, the most represented). The chemical reactivity of the various classes of aldehydes is discussed. Alkenals and 4-hydroxyalkenals are the most reactive aldehydes. The Michael addition to -SH groups of low molecular weight thiols, proteins and enzymes (to give an adduct in which the aldehyde is bound through a thioether linkage to the protein) is by far the main reaction. The in vivo formation of aldehydes in the liver of animals intoxicated with agents that promote lipid peroxidation has been shown in two studies. In the first study, evidence was forwarded for aldehydes (very likely alkenals) bound to the liver microsomal proteins of rats intoxicated with CCl₄ or BrCCl₃. In the second study, 4-hydroxynonenal and a number of other aldehydes (alkanals and alkenals) were identified in liver extracts from bromobenzene-intoxicated mice. The biological implications of the finding of 4-hydroxynonenal and other toxic aldehydes in experimental models of cell injury induced by pro-oxidants are discussed. Finally, recent knowledge on the metabolic pathways for aldehydes, and in particular for 4-hydroxynonenal, is reported.